cdp b_lualhati, anna lourdes (1)_norestriction

For exclusive use of Lualhati, Anna Lourdes 1

PART B

Fresenius Medical Care Asia Pacific CDPB112013


INTRODUCTION This course provides an update on the current trends in Renal Replacement Therapies, as well as ensuring that the RN has a sound foundation in understanding of the principles underpinning RRT. This ensures that the RN has effective, flexible knowledge in order to deliver, adjust and evaluate care. The scope of this course includes CKD, dialysis and its application to practice, pharmacology, Fluid assessment and management, EBP and Clinical Practice Guidelines, vascular access management, clinical assessment and nutritional management of the chronic hemodialysis patient population. Sound clinical decision-making is based on theoretical understanding, so for the Nephrology/Dialysis nurse it is paramount to have this knowledge that is flexible to adapt and deal with the myriad of complex issues in the chronic dialysis therapy. Profile of ESRD population: Chronic care management of persons with ESRD has been available for more than 40 years. With increasing incidence and prevalence of ESRD (Access the websites below) there is increased demand for RRT service. The incidence rate is highest in Taiwan, with the Mexico second, followed by USA and Japan. Also of significance is that Diabetes has a strong association with the renal etiology or as co-morbidity (Malaysia has the highest incidence of Diabetic Nephropathy globally). Thereby the challenge for renal professionals includes:

1. Increasing ESRD population requiring RRT 2. Increasing numbers of patients with co-morbidities (e.g. Diabetes) 3. Further an aging of the ESRD population.

These factors contribute to increases in patient hospitalizations, adverse events during dialysis and mortality of the ESRD population, posing many challenges for nurses in the field of Nephrology care. The Role of the Dialysis Nurse is a reflection of the needs of the dialysis population as well as the professional expectations. The professional bodies out line these expectations (e.g. RENAP, ANNA) and include means of determining knowledge (courses, examinations), clinical competencies and the relationship between the Medical and nursing teams in order to deliver best outcomes for the dialysis population. http://www.usrds.org/adr.htm USA Renal registry http://www.anzdata.org.au/ Australia and NZ Renal Registry http://www.anzdata.org.au/anzdata/AnzdataReport/ Summary of Dialysis profile in Australia/NZ 28thReport/files/Ch04Dialysis.pdf You may also find the following websites useful to access both for this segment of the course and for the Program overall. I would suggest adding them to your Favorites or Bookmark: -


For exclusive use of Lualhati, Anna Lourdes 3 DOPPS (Dialysis Outcomes Practice Patterns Study): www.dopps.org Hypertension Dialysis and Clinical Nephrology: www.hdcn.org International Society of Nephrology: www.isn-online.org

Renal Replacement Therapies (RRTs) ability to actually replace renal function is incomplete, to varying degrees. These limitations afford the opportunity for pharmacological and alternative therapies to supplement the dialysis and transplant modalities that incorporate the RRTs. What is the Aim of Renal replacement therapy? The Aim is to replace (and in some cases restore) renal function by Dialysis. However there are many functions of the renal system including: -

Fluid and electrolyte homeostasis Acid-base balance Blood pressure control (in part through Renin release from the Juxta-Glomerular Apparatus) Vitamin D hydroxylation Release of Erythropoeitin and maintenance of hemoglobin.

The achievement of these functions is through Filtration, secretion, reabsorption/absorption and excretion. However some of these functions are not achieved by dialysis; Vitamin D hydroxylation and Erythropoietin production and release. Please complete the Renal Anatomy and Physiology section as we present the information in class. The session highlights the intricacy of renal function together with the dependence on renal function for maintenance of normal cellular function and life.

CHANGING PARADIGM OF PRACTICE IN RRT CHANGING PRADIGM OF PRACTICE IN RRT The challenges in RRT practice have been identified. The challenges posed offer an opportunity to refocus on the critical components that contribute to a greater likelihood of increased well-being and quality of the life gained, for individuals with ESRD. This does not mean discarding our current practices, but using this knowledge and practices to answer more effectively the needs of ESRD clients in the short and long-term. It also means becoming more clients centric. Using this framework, we are able to work towards balancing the science with the psychosocial needs of the client. In partnership with the clients we are also able to continuously refine/adjust the prescription of care, and motivate active participation with their disease management. Fresenius Medical Care Asia Pacific CDPB112013


Thereby rather than just focusing on the quantification, these measures now are tools to achieve and then further measure the degree of recovery/improvement that occurs with that dose or prescription of therapy. We will now discuss the pathophysiology of CKD and its impact on the individual physiologically and psychologically. HOMEOSTATIC MECHANISMS

1. Kidneys The kidneys are vital for fluid and electrolyte balance in the body. The kidneys normally filter approximately 170-180 liters of filtrate per day (Glomerular Filtration Rate (GFR)), which enables the body to continuously check and titrate / adjust the physiological needs of the body. A human only excrete 1.5 to 2.0 liters per day of urine, and reflects the energy required by the kidneys to reabsorb approximately 99% of the fluid that it has filtered. Although the kidneys respond autonomously to concentration gradients and other physiologic stimuli, they are also responsive to hormones like Aldosterone (sodium retaining), ADH (Anti diuretic hormone) and Renin (Renin Angiotensin-aldosterone system R-A-A-S) that maintains blood pressure, GFR and thirst. The kidneys are responsible for the following: -

a. Regulation of ECF volume and electrolytes: ADH, RAAS, Aldosterone, Atrial Naturietic Factor. b. Regulation of electrolytes in ECF by selective retention and/or secretion (excretion) c. Regulation of pH by excretion of hydrogen ions and reclamation (absorption) of d. Bicarbonate: Carbonic Anhydrase is an enzyme utilized in this process located in the renal

tubule (proximal and distal convoluted segments). e. Excretion of metabolic wastes: protein metabolites, cellular wastes, drug metabolites and

other toxic substances. In clients with renal dysfunction these processes are compromised with resultant fluid and electrolyte imbalance, which contributes to some of the clinical manifestations associated with renal failure. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 5 Q. Think about your clients in the Dialysis Centre and their clinical manifestations, how are they related to fluid and electrolyte imbalance?

2. Lungs The lungs are involved in pH homeostasis through the elimination of excess hydrogen ions. The lungs under the influence of the medulla act promptly to correct derangements in acid-base balance by regulating the carbon dioxide level (potential weak acid Carbonic acid) in the ECF. The kidneys and lungs work together to maintain the ECF pH of between 7.35 - 7.45, which is critical for normal cellular activities.

3. Pituitary Gland The hypothalamus produces the Anti Diuretic hormone, which is then stored in the posterior pituitary gland. This hormone is released in response to ECF osmolarity and pressure receptors, located in the atria of the heart and blood vessels. The release of the ADH is more sensitive to changes in ECF (plasma) osmolarity. The ADH changes the permeability of the late segment of the distal convoluted tubule and the collecting duct of the nephrons. Fluid then fluxes across the more permeable membrane because of an osmotic gradient across the membrane (between the interstitial and tubular fluid). The result of ADH secretion is reduced urinary output and fluid retention.

4. Adrenal Glands Adrenal glands secrete Aldosterone from the adrenal cortex. This hormone increases sodium reabsorption form the distal tubule of the nephrons in exchange for increased potassium secretion and excretion. The result of Aldosterone secretion is sodium retention, lowering of plasma potassium and fluid retention as a result of sodium reabsorption. The regulators of Aldosterone secretion include sodium and potassium concentration, and Angiotension II (the result of Renin secretion) that is the primary regulator of Aldosterone secretion.

5. Parathyroid Glands The parathyroid glands (PG) secrete intact Parathyroid Hormone (iPTH) which increases osteoclast activity that increases the resorption of calcium and phosphate form the bone. The PG is sensitive to the ionized calcium (free unbound calcium) in the blood and its role is to increase the plasma level of calcium, primarily through resorption of bone analytes. The iPTH also increases phosphate excretion across the nephrons tubule. The PG is controlled not only by ionized calcium levels but also by Vitamin D (active vitamin D; I, 25 Dihydroxycholecalciferol) which acts as negative feedback to iPTH secretion. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 6 ROLE OF MAJOR ELECTROLYTES

1. SODIUM Sodium is major ECF cation and provides osmolarity to body fluids. Serum sodium level relates closely to the fluid status of the client. When evaluating the biochemical serum sodium value, the nurse should always evaluate the fluid status through physical examination. The serum sodium, because it is the major ECF cation is prone to hemodilution, meaning that if the client has a large ECF volume there will be dilution of those ions and analytes found predominantly in the ECF (Sodium, Hemoglobin, Albumin). If the client is volume depleted these same analytes can be hemoconcentrated.

For every 3 Mm of serum sodium rise above the normal range, equates to approximately 1 liter deficit of body water.

Elevated BSL (Blood Glucose Level) attracts fluid from the cells into the ECF; dilutes the plasma Sodium. Every 3-4 Mm/L increment increase in plasma glucose causes fluid to move out of the cells and dilute the plasma sodium by 1 Mm/L. This effect may not be observed as the increase in fluid shift results normally in increased diuresis.

Q. Analyze your clients last blood result and look at their Sodium, BSL (if diabetic) and correlate these parameters with the fluid status. How was their fluid volume implicated in the biochemistry?

2. POTASSIUM Potassium is the major intracellular cation and is not influenced by changes in fluid status in the ECF. The body stores the potassium within the cells; therefore the ECF potassium level is only a reflection of total body potassium level. Potassium control is a function of the kidney and adrenal gland. Hyperkalemia occurs when there is renal impairment and if there is deficiency of, or interference with the action of Aldosterone. Potassium levels in the ECF are affected by cell destruction/resolution e.g. cell destruction and damage results in the liberation of potassium thereby increasing the plasma (ECF) level of potassium. Artefactual causes can result in derangements of potassium and include: -

A hemolyzed sample An old blood sample A sample of cooled blood prior to separation (spinning of blood) Contamination with K.EDTA Contribution from very high platelet or white cell counts.

Alterations in acid-base balance also significantly affect plasma potassium levels. Acidosis results in a shift of potassium from the cell, increasing the ECF potassium. Alkalosis results in a shift of potassium into the cell, thereby decreasing the serum level. On average for every 0.1 unit change in arterial pH there is a reciprocal change in 0.5 Mm/L of plasma potassium. Insulin promotes cell entry of ECF potassium, temporarily lowering the serum potassium level. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 7 Q. What is the role and function of potassium in human physiology? Analyze your clients potassium level pre-dialysis and their bicarbonate level. Does their potassium level change with their acid-base status?

3. BICARBONATE The plasma bicarbonate level is the most practical index of the degree of acidosis in ESRD clients. A low bicarbonate level may be due to: -

Accumulation of acid anions in the blood, buffered by bicarbonate, resulting in a lower bicarbonate level due to the consumption of this buffer during the process.

Metabolic processes generate approximately 60 Mm of Hydrogen ions per day, which can be increased it client is catabolic ( rate of hydrogen ion production) or has a high protein intake.

Failure to replace enough bicarbonate consumed in physiologic processes, during the dialysis procedure.

4. CALCIUM

Calcium is absorbed from the gut under the influence of active Vitamin D (1, 25 Dihydroxycholecalciferol). Calcium is important for normal musculo-skeletal function, cardiac conduction, neurological conduction and function and blood vessel dynamics. Total calcium in plasma is the sum of the ionized (free, unbound calcium; 47%) and the nonionized (53%) calcium components. The nonionized portion consists of calcium bound to albumin (40%) and that chelated to anions like Phosphate and citrate (13%). To evaluate the actual calcium level, need to know the serum albumin level and apply the following: -

Serum calcium may be corrected for variations in albumin by estimating that a change in serum albumin of 10g/L will change the total serum calcium by 0.8 mg/dL (0.2 Mm/L). The binding between calcium and albumin is also affected by pH. Alkalosis increases the binding of calcium to albumin. Other factors that can acutely lower the ionized calcium levels are for example, increased levels of lactate, bicarbonate and phosphates.

5. PHOSPHATE Phosphate is found in the phospholipid membranes of cells. Thereby any cellular destruction will result in a factitious high phosphates level in the plasma. Phosphate levels are evaluated in relation to the calcium since there is an inverse relationship between the 2 analytes (e.g. an increased phosphate level results in a lower ionized calcium level, as the free ionized calcium binds with the free phosphate). Like potassium, phosphate moves into the cell with insulin secretion. Phosphate levels in plasma of clients with ESRD can also be raised because of reduced renal clearance and protein intake (phosphate load). In ESRD clients, maintenance of serum phosphate remains difficult and is poorly managed by dialysis as most phosphate is located intracellular and takes time to move to the ECF compartment for clearance. Management includes diet modification and pharmacological agents. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 8 BIOCHEMISTRY & PATHOLOGY IN ADVANCED PRACTICE Biochemical analysis forms a major component of evaluating the effectiveness of the RRT. Normal kidney function maintains fluid and electrolyte homeostasis, thereby part of the RRT role is to replace this function with biochemical analysis forming a component of the outcome measurement. Importantly when analyzing the biochemistry the blood is representative of the total body balance per electrolyte under analysis. Therefore accurate sampling of blood is critical for effective analysis, interpretation and care planning.

The major extracellular cation is Sodium, with Potassium, Calcium and Magnesium contributing to the extracellular cation pool. About 90% of the ECF osmolarity is determined by the sodium concentration. The sodium value can be diluted by changes in blood sugar value and protein values that also are osmotic agents and in ESRD patients with fluid excess. The major intracellular cation is Potassium, with Magnesium and Sodium completing the total cation pool. The major extracellular anion is Chloride (found usually as Sodium Chloride), and Bicarbonate, phosphate, sulfate organic acids and proteinates. The intracellular anions are predominately the phosphates and sulfates, with Bicarbonate and proteinates further contributing to the negative charge pool. WHEN ANALYZING THE FOLLOWING ELECTROLYTES CONSIDER THE FOLLOWING: - Sodium CLOSELY RELATED TO FLUID STATUS.

For approximately 3 Mm increase in Sodium above normal range = deficit of approximately 1L (Adults)

BGL increase and Hyperlipidaemia both artificially reduce the Serum Sodium value by dilution because of the osmotic pull of fluid from intracellular and interstitial fluid spaces.

InterstitialSpace

VascularSpace

IntracellularSpace

Extracellular space Intracellular space

Capillarymembrane interface

Lymphaticsystem

Cellmembraneinterface

(5 Litres) (10 Litres) (25 Litres)

Body compartments


For exclusive use of Lualhati, Anna Lourdes 9 Potassium ALTERATIONS IN ACID-BASE BALANCE significantly affect potassium distribution.

Acidosis shifts potassium from the cell, increasing the serum Potassium and Alkalosis results in a decrease in Serum Potassium.

For every 0.1 unit change in arterial pH results in a reciprocal change of 0.5 Mm/L in serum Potassium level.

Insulin promotes Potassium movement into the cell and temporarily lowers the serum Potassium. Hemolysis, Leukocytosis and increased platelet counts can cause raised serum Potassium

levels, through the release of intracellular Potassium into the plasma. Bicarbonate Often represented as Carbon Dioxide content (Total bicarbonate and carbonic acid in venous blood) represents the consumption and generation of buffer, thereby reflecting the acid-base needs, consumption, production and utilization of buffer. Phosphate - Like potassium, because it is found predominately intracellularly, can be artificially raised when cells are hemolyzed.

Phosphate levels are evaluated in relation with calcium, as there is an inverse relationship between the 2 parameters; raised phosphate will lower the calcium level (significantly the ionized calcium this is important for ESRD population as will further stimulate the Parathyroid gland (PG) to release iPTH).

Insulin promotes the movement of extracellular phosphate into the cell, thereby temporarily lowering the serum phosphate level.

Cell recovery will utilize > amounts of phosphate and present a lower serum phosphate. Calcium - TOTAL CALCIUM = OF IONISED (47%) AND NONIONISED CALCIUM (53%). The nonionised calcium = 40% bound to albumin and approximately 13% chelated to anions.

Total calcium can be corrected for variations in serum Albumin; a 10g/L change in albumin will change the total serum calcium level by approximately 0.2 Mm/L.

This needs to be modified with variations in pH; Alkalosis increases the binding of calcium to albumin thereby lowering the ionized calcium. Raised serum Phosphate or Bicarbonate levels also lower the calcium value.

Creatinine - INDICATOR OF RENAL DISEASE

Trend analysis of serum Creatinine is probably more important than a single result. Reflects the body muscle mass as Creatinine s generated from creatine phosphate; if individual

has large muscle mass they will generate > amount and have a higher normal as opposed to an elderly person with reduced muscle mass may have a lower normal. Thereby assessment over time is paramount.

Also used to assess muscle mass status based on trend analysis Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 10 Urea - Urea is the end-product of cellular and protein degradation and metabolic processes. Raised serum Urea reflects one or more of the following: -

Increased catabolism; starvation, trauma, bleeding into the gut, or catabolic drugs (Prednisolone will increase the serum urea level unrelated to protein intake)

Relates to exogenous protein intake Also reduced renal function (GFR) will result in an increased serum Urea. An increase in

ADH (Antidiuretic Hormone) will also result in a raised serum Urea > than the rate of increase in the serum Creatinine. Albumin - Decreased serum Albumin will reduce the colloidal osmotic pressure in the intravascular compartment, resulting in the presence clinically of edema > than the fluid imbalance.

The half-life of Albumin is approximately three weeks, often representing a disparity between the biochemical analysis and clinical presentation.

Often this parameter is used for nutrition assessment but is not considered to be a major determinant of nutrition assessment.

A lower serum Albumin may occur in conjunction with a raised Serum Ferritin (more specially C-Reactive Protein) reflecting an inflammatory condition and consumption of proteins in the process.

Albumin like sodium is prone to dilution effects lower levels noted in fluid excess, with fluid removal albumin level increased until redistribution of fluid occurs across the compartments.

Critical balance of electrolytes and osmolarity is required for normal cellular and enzymatic functions and actions. PRINCIPLES & PRACTICE IN READING BIOCHEMISTRY REPORTS

Always read biochemistry together with your physical assessment of the client Assess the biochemical parameter (analyte) over time. i.e. trend analysis. Never look at

one result in isolation. Determine if any analyte may be causing misleading result. For example if BSL raised

then it will lead to hemodilution of other major intravascular analytes. Determine if the analyte outside of target range is reflected by clinical state or by error in

sampling of specimen and/or storage of specimen.


For exclusive use of Lualhati, Anna Lourdes 11 A Framework for evaluation of biochemistry, including the importance of reviewing the patient together with the biochemistry, rather than in isolation.

FRAMEWORK FOR ANALYZING BLOOD PATHOLOGY FOR ESRD POPULATION

PARAMETERS ANALYSIS A. ADEQUACY OF DIALYSIS

Urea SpKt/V URR

Urea pre dialysis can indicate level of nutrition and adequacy of dialysis; generation of urea from last dialysis. spKt/V and URR analyze the adequacy of dialysis / clearance of solute.

B. ANAEMIA Hb TS% Ferritin

Hemoglobin is the indicator for management of anemia. TS% - Measure of plasma circulating iron relative to total iron-binding capacity. Transferrin is the plasma protein that transports iron. Ferritin reflects the stored iron; unless Ferritin levels are > 100 ng/mL response to EPO will be < effective and of short duration. Levels are kept > than this through iron infusions.

C. ACID BASE BALANCE

TCO2 Potassium Sodium

TCO2 the consumption of buffer/ available buffer in the body; high protein intake, catabolic state or inadequate dialysis in result in low TCO2 levels. May also be complicated further if patient had chronic lung disease and / or id fluid overloaded unable to provide some respiratory compensation. Potassium deviations reflect either body losses/gains or redistribution within the body. Hypokalemia may be related with reduce intake, or increased losses (diarrhea, vomiting, RTA, diuretics, IV fluid without (Potassium replacement). Redistribution of potassium with alkalosis = Hypokalemia. Hyperkalemia results from reduced renal excretion, intake > output, cell damage/trauma = Hyperkalemia. In acidosis potassium moves from the cell to the plasma = Hyperkalemia.


For exclusive use of Lualhati, Anna Lourdes 12 D. NUTRITION

nPNA Albumin TCO2 Pre Urea Phosphate

When analyzing for nutritional status need to evaluate the nPNA which protein intake (grams/Kg/day). Intake can be broadly measured by Albumin, Pre dialysis Urea and phosphate. Analyze the similarity of the parameters and determine whether related to dialysis adequacy or nutrition. TCO2 may be lowered due to high intake of protein (related to nutrition) other factors for a low level have been discussed previously.

E. BONE MANAGEMENT

Calcium ionized Calcium Phosphate Calcium x Phosphate IPTH Alkaline Phosphatase (ALP)

Calcium and phosphate are both actively involved in bone mineralization. Calcium also has a role in cardiac conduction and clotting and muscle contraction. When phosphate levels are raised the free ionized calcium tends to bind with the excess phosphate. PG is sensitive to ionized calcium, therefore as it falls, PTH is released, and increasing the ionized calcium. This is unless the phosphate level remains raised, then the released calcium is taken up by the phosphate. Calcium phosphate product reflects the degree of metastatic calcification, due to high levels of phosphate binding the ionized calcium and depositing as complexes outside of bone.

The analysis of the patients biochemistry provides the opportunity for a more focused clinical examination and history taking, but should never replace the need for a clinical assessment. In a latter section there are some Clinical Case studies for you to analyze using this framework. Also provided is a Conversion table that includes ESRD targets for most of the parameters. These have been based on the CPGs (KDOQI and CARI)



LABORATORY VALUES /TARGTES FOR ESRD POPULATION (GUIDELINES)

BLOOD CHEMISTRY CONVERSION FORMULAE

ACCEPTABLE ESRD VALUES

ALBUMIN g/L 10 = g/dL 40 g/L ALK PHOSHATE (ALP)(SAP)

L = U/L 35 125 U/L

BLOOD GLUCOSE LEVEL mg/dL 18 = mmol/L >4.0 < 9.0 mmol/L< 180mg/dL

CALCIUM mg/dL 4 = mmol/L 8.810.8 mg/dL CALCIUM PHOSPHATE PRODUCT

< 60 ( mg2/dL2) < 4.8 (mmol/L)

CREATININE ( Pre-dx ) Mg/dL x 88.4 = mmol/L VARIABLE ON BODY MASS & SEX CREATININE (post-dx ) Mg/dL x 88.4 = mmol/L VARIABLE ON BODY MASS & SEX FERRITIN ug/dL = ngm/L 100 < 800 ng/mL or ug/L HAEMOGLOBIN/HEMATROCIT

HCT % 3 = Hb g/dL M/F : 1112 g/dL M/F :33 36 %

HBA1C 6 8 % HEPATITIS B ANTIGEN 50 IRON ug/dL 5 = umol/L F : 49 151 ug/dL M : 53 167 ug/dL MAGNESIUM 0.7 0.95 mmol/L POTASSIUM mmol/L = mEq/L 3.5 5.5 mmol/L PHOSHATE (INORGANIC) mg/dL x 0.33 = mmol/L < 5.5 mg/dL IPTH Pm/L 15 30 pm/L SGPT (ALT) 5 40 U/L SGOT (AST ) 5 40 U/L SODIUM mmol/L = mEq/L 135 149 mmol/L TRANSFERRIN SATURATION

IRON TIBC = TS % 20 55 %

TOTAL CO2 ( HCO3) mmol/L = mEq/L >20 < 24 mmol/L (Pre dx ) TOTAL IRON BINDING CAPACITY

ug/dL 5 = umol/L 280 400 ug/dL

UREA (pre-dx ) Mg/dL 6 = mmol/L >120 < 240 mg/dL (>20 < 40 mmol/L) UREA (post_dx ) Mg/dL 6 = mmol/ >70-75 % reduction URATE Mg/dL 0.06 = mmol/ 2.5 8.0 mg/dL


For exclusive use of Lualhati, Anna Lourdes 14 BODY SYSTEM ALTERATIONS IN CKD IMPACT OF CKD AND UREMIA The impact of CKD on the body and individual is significant; ultimately affecting every body system together with the Chronicity of the disease contributing negatively to their perceived health related quality of life. The Figure 1.5.1.1 illustrates this impact on the individual. The progressive loss of renal function occurs over months to years, with patients usually presenting late in the disease process (due to minimal overt symptoms) with reduced opportunity to control and delay the progression to ESRD. In fact CKD has a classical natural history, availing an opportunity for intervention at secondary and tertiary prevention levels. See Figure 1.5.1.2.

Every body system is affected in CKD with the major impact (morbidity and mortality) on the cardiovascular system. This is not just as a consequence of fluid imbalance and the RAAS imbalance but the involvement of an inflammatory state now recognized as co-existent with CKD and will be discussed related to uremic toxins and the pathophysiology of CKD. Other important body system alternations include anemia, metabolic bone disease, and malnutrition.

Peripheral Neuropathy Paresthesias Motor weakness



KDOQI NKF STRATEGY FOR STAGING CKD

Primary Prevention: Screening

Secondary Prevention Delay the progression

Tertiary Prevention: reducing the complications

Strategies to slow the progression of the disease:

Management of uremic symptoms Prevention or correction of co-morbid conditions e.g. cardiovascular risk factors and correcting

the anemia. Psychological and physical preparation for RRT Scheduled, timely initiation of RRT

TREATMENT TO SLOW PROGRESSION OF CKD

The progression of CKD can be delayed if recognition is early and treatment adherence is achieved. The natural history of the CKD phases can be from months years decades, influenced by the before mentioned factor together with the cause of the CKD and the general well-being (health) of the individual. Often the signs and symptoms Of CKD are late in presentation and the patients are diagnosed at CKD 4-5 phase offering little opportunity to delay the progression to CKD5 and the need for renal replacement therapies. However the importance of early recognition not only delays the progression and also increases the likelihood of ultimately better outcomes for the CKD 5 patient. A great deal of emphasis has been placed on pre-ESRD (CKD5) management to achieve this target. Primary Prevention: SCREENING Secondary Prevention: Delay the progression Tertiary Prevention: Reducing the complications

0%

50%

100%

0 1 2 3 4 5 6 7 8 9 10Time (years)

% o

f kid

net f

unct

ion

AA treated

Treatment


For exclusive use of Lualhati, Anna Lourdes 16 INFLAMMATION The Oxidative Stress Story Oxygen, particularly certain chemical forms of oxygen, is highly toxic to biological entities. As evolution proceeded alongside increasing atmospheric O2 the primitive organisms alive then must have evolved ways to neutralize oxygen and species of bacteria with a highly developed O2 resistance somehow closely related themselves to other evolving organisms. And they persist today in our cells: not as viable bacteria but as a cell organelle called the mitochondrion: our cells have 100s to 1000s of mitochondria more if the cell is more metabolically active. These mitochondria even have their own DNA a residue of the original bacterial DNA and it does work as DNA, controlling various metabolic pathways mainly involved in converting toxic O2 into useful energy. Interestingly, we inherit our entire mitochondrial DNA. O2 is highly toxic and yet is essential to metabolism and energy generation. To deal with this dilemma the body has developed systems for transporting and storing oxygen in a way that the oxygen toxicity is neutralized. We breathe atmospheric oxygen via or lungs where it is immediately transferred to and bound to hemoglobin in red blood cells neutralized. Only tiny amounts of free, dissolved oxygen are found in blood. At the cell, the O2 is transferred from Hb to other molecules which usually contain one or more heme proteins and these proteins either transfer the O2 to the mitochondria (those clever bacteria of old) or may temporarily bind the oxygen in storage form. The mitochondria immediately get to work turning the O2 in water and carbon dioxide by oxidizing sugars and lipids and generating energy and heat along the way (see later). The mitochondrial oxygen sump is fairly effective but about a percent or so of the oxygen processed does actually leak out as what are called radical oxygen species (ROS). The leak rate increases when cells are very active metabolizing food substrates (like when we overeat). There is another situation where there is a potential for a large release of ROS when white blood cells called phagocytes attack invading bacteria or other foreign material. The white cells actually generate large amounts of ROS and other free radicals to kill the bacteria bit like our using bleach or other oxidants to kill germs. In this case lots of ROS leak into the surrounding tissue and the circulation and could do a lot of collateral damage. Not surprisingly, there is a balance various antioxidant chemicals and enzyme systems in cells, blood and tissues. Normally antioxidants are sufficient to counteract a systemic effect of ROS. Deficient antioxidant systems or excess ROS or their combination leads to a state known as oxidative or oxidant stress. Free radicals and ROS cause disease by altering the structure and function of essential biomolecules. Such changes may be reversible or irreversible. Oxidative alteration may be reversed but in many cases oxidation proceeds to a stage where it is not reversible and produces permanent long-lived (sometimes called advanced) oxidation products. In some cases, e.g., AOPPs and AGEs, the oxidation products retain their own pro-oxidant potential and therefore promote further oxidative stress. In recent years many oxidative markers have been measured in patients with CKD and dialysis patients. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 17 Uremia is associated with evidence of increased oxidation of all biomolecules and in some cases the markers of oxidation reach extremely high levels compared to healthy controls. Additionally, there is evidence of reduced (or consumed) levels of both plasma and cellular antioxidant system. Uremia is a state of oxidative stress and as the stages of CKD advance, the intensity of oxidative stress also increases. However, certain markers of oxidative stress are present even before there is much loss of residual renal function suggesting that oxidative stress is not purely a failure to excrete oxidants but that the kidneys may have some general, protective antioxidant function. A uremic toxin that has received considerable attention in recent years is homocysteine (Hcy). Hcy is not per se an oxidant but seems to be intimately related to oxidative processes e.g., in endothelial and vascular cells, which may explain its association with increased risk of atherosclerosis. Liver cells respond to pro-inflammatory cytokines (particularly IL-6) by altering their production of proteins. Activated by IL-6 hepatocytes increase the synthesis and release into the blood of c-reactive protein (CRP), serum amyloid A protein (SAA), fibrinogen (a clotting factor) and many others. These proteins are known as acute phase proteins (APP) or acute phase reactants. At the same time, the liver cells reduce their synthesis and release of other proteins, most notably albumin but also pre-albumin and transferrin. Liver production of cholesterol is also reduced. Thus the APR is characterized by elevated concentrations in plasma of CRP, fibrogen etc. and reduced concentration in plasma of albumin and cholesterol. Uremia is a state of chronic, low-grade activation of the inflammatory system. Typical findings confirm elevated plasma levels of inflammatory cytokines (e.g., IL-6) and acute phase proteins (e.g., CRP) and suppressed action of inflammation-modulating or anti-inflammatory mediators. Chronic inflammation in CKD is not the result of a single factor activating the cellular and humoral inflammatory pathways.

CKD AND THE INFLAMMATORY CONSEQUENCES

Atherosclerosis

Dyslipidemia

Inflammation

Thrombosis

Cytokines

GrowthFactors

Homocysteine

Nitricoxide

Metabolicdisorders

L-arginine

ADMA

Endothelial Injury

APR

Free radicalsCarbonyls

GlycoxidationAGE products

Calcification

Fetuin

Lipoxidation

Factor D

It is certain that some (and possibly many) uremic toxins can activate inflammatory pathways or suppress inflammation modulating factors but it also possible that the kidneys have a more generalized anti-inflammatory function which somehow depends on intact kidney tissue mass.


For exclusive use of Lualhati, Anna Lourdes 18 As excretory function declines and kidney mass is lost, a pro inflammatory state results. The importance of chronic inflammation in CKD is that the markers of this state (e.g., high IL-6 or CRP) are strong predictors of morbidity and mortality and in particular mortality related to atherosclerosis and cardiovascular disease. The Message: The loss of renal function results in a total state of dysfunction from the cellular metabolic level that leads to a continuous decline is effective cellular function resulting in increased demand and dysfunctional responses, increased energy demands and altered transport mechanisms. The message to take away from this discussion about CKD, uremia (and dialysis) is to stop thinking of CKD as a disease where you can simplify to cause-effect-treat. Its a complex of disease states with physiological adaptations and pathophysiological maladaptations where eventually the sum of maladaptation imposes a risk of death. Uremia in the sense of retained uremic toxins is only a part of the complex and, as we are now learning, we have to change the focus (e.g., to inflammation, oxidative stress, dysmetabolism, cardiovascular risk management) if we are to make additional progress towards better patient outcomes. Therefore the process is not a simple loss of renal function = uremic symptoms, but a complex disruption in homeostasis that occurs at the cellular level.

CKD TREATMENT OPTIONS When renal function is progressively loss there are adaptive mechanisms that partially compensate as more function is lost the load becomes > and symptoms (that we have now recognized are related to CKD) becomes present (refer back to KDOQI staging of CKD (1.5.1.2). Finally when enough renal function has been lost and CKD5 criteria have been reached then the treatment options include:

1. Palliative care 2. Dialysis (usually Hemodialysis, but in some countries more patients are encouraged to

commence with Peritoneal dialysis self-care modality) 3. Preemptive transplant


For exclusive use of Lualhati, Anna Lourdes 19 See the diagram below which highlights the options and the patient flow regarding treatment options.

Modality of renal replacement therapy

No Treatment

Hemodialysis Peritoneal Dialysis

Dialysis Pre-emptive Transplant

ESRD

Secondary Transplant

FLUID AND ELECTROLYTES In nephrology practice fluid and electrolyte assessment and management is critical. As the kidneys are essential for fluid and electrolyte homeostasis in the body, it is not surprising that when caring for clients with ESRD nurses need to be well versed in their understanding of fluid and electrolyte balance. In adults, approximately 60% of the body weight is comprised of fluid. The distribution of fluid and electrolytes within the body is considered as either intracellular or extracellular. Extracellular is further divided into Intravascular (Plasma) and Interstitial. The intracellular fluid, generally contributes to 40% of body weight and the intravascular 5% and the interstitial 15%. The fluid contribution to body weight varies with age, with the newborns fluid contributing to 70-80% of weight; puberty to 39 years of age 60% (males) and 52% (women); 40 60 years 55% (males) and 47% (women) and > 60 years males weight is 52% and womens weight 46% fluid. The noted difference in gender is related to fat contribution to weight increasing with age. This is one of the main reasons that both the young and older persons are vulnerable to fluid imbalances.


For exclusive use of Lualhati, Anna Lourdes 20 Q. Think about your clients in the Dialysis Centre. How would you interpret the fluid status of an obese client? Why?

Volume (L) It is important to understand the volume and distribution of fluid when caring for persons with renal dysfunction, and specifically those undergoing dialysis. When we are dialyzing individuals with ESRD the fluid is removed initially from the intravascular (Plasma) compartment, with excess fluid then refilling the vascular compartment from the interstitial compartment through hydrostatic pressure forces. This is achieved through a capillary network that allows the filtration to occur. We term this physiologic process capillary refilling. Also we need to think of these compartments when we are undertaking our physical assessments. When we are assessing and evaluating the clients Ideal Dry Weight we evaluate the presence and degree of peripheral edema, as determined by pitting edema. This indicates fluid excess that has spilled over into the interstitial space from the vascular compartment and presents as trapped fluid in the tissues. Note that the fluid excess in the vascular compartment presents as hypertension. Q. In the Dialysis centre review your clients blood pressure and relate to their fluid status. Does it always correlate? Why not? ELECTROLYTES Electrolytes are ions in solution and in humans there is general electrical neutrality between compartments. The charges of the ions are either positive (captions) or negative (anions). The major electrolytes in humans are sodium, potassium, calcium, chloride, phosphate and bicarbonate. Captions include; Sodium, Potassium and Calcium. Anions include Chloride, Bicarbonate and Phosphate. The Major extracellular cation is sodium, while the major intracellular cation is potassium. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 21 PLASMA ELECTROLYTES Captions Sodium 135-144 Mm/L Potassium 3 5 Mm/L Calcium 2.2 2.6 Mm/L Magnesium 0.6 1.0 Mm/L Total = 152 Anions Chloride 100 Mm/L Bicarbonate 22 30 Mm/L Phosphate 0.6 1.3 Mm/L Organic salts, Sulfate and other anions Total = < 152 (anion gap of 8-16) INTRACELLULAR FLUID ELECTROLYTES Captions Potassium 150 -160 Mm/L Magnesium 16 20 Mm/L Sodium 10 Mm/L Total Captions = 190 Anions Phosphates & sulfates 150 Mm/L Bicarbonate 10 Mm/L Other Anions 20 - 30 Total Anions = 180-190 The body expends energy to maintain this balance of captions and anions together with the greater concentration of sodium in the extracellular fluid. The body achieves this by cellular Sodium-potassium pumps that require energy derived from ATP ADP conversion. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 22 FUNCTIONS OF BODY FLUIDS Fluid and electrolytes move in between the body compartments by many processes, some passive some active, but they primarily include the following: -

1. Osmosis: - The movement of fluid from low solute concentration to high solute concentration. Certain solutes/electrolytes have high osmotic properties that attract fluid and encourage fluid movement. These solutes include sodium, glucose and proteins. An example is when a Diabetic client has high blood sugar level then the client complains of thirst, increasing the intravascular volume that then drives the Glomerular filtration rate that facilitates some clearance of glucose.

2. Diffusion: - The movement of solute from a high solute concentration to a low solute concentration. Diffusion can be passive, depending on the concentration gradient across the Semipermeable membrane, or can be active utilizing energy derived from ATP-ADP conversion; Na+- K+ pumps are an example of active diffusion, that use energy to move solutes across the cell membrane to maintain cell integrity.

Low solute concentration

Movement of Fluid

Semi permeable membrane

Solutes moves from side of higher concentration to side of lower concentration across semi-permeable membrane

(Larger solutes move slower and there is membrane resistance)



3. Filtration: - The movement of fluid together with dissolved solutes from a region of high pressure to that of lower pressure; the force behind it is hydrostatic pressure. The transfer of fluid and solutes across the arterial capillaries to the interstitial fluid is an example of filtration. In this example the pressure inducing the filtration is that of blood pressure created by the heart (pump pressure) and the vessel diameter.

UREMIC TOXINS The term uremia is also used to describe the illness the accumulation of symptoms (patient complaints) and signs (observed abnormalities) - that may occur in patients with chronic kidney disease (CKD) and for which a laboratory marker of this illness is excess urea in blood. It is appropriate to use the term uremia in both senses 1) simply to indicate high blood urea level and 2) to summarize a (complex) illness that is association with impaired function of the kidneys. The uremic toxins so far identified can be classified in various ways. Some are derived mainly from the diet and are exogenous: phosphates derived mainly from dietary protein are an example. Others are endogenous produced when substrates are metabolized: urea is a product of protein metabolism; creatinine is the product of metabolism of muscle creatine phosphate. Others still are the result of chemical alteration of normal chemicals: e.g., molecules changed by exposure to reactive oxygen in oxidative stress. The classification of uremic solutes by size is into small, middle and large: the actual classifications vary somewhat but the ranges indicated above provide a sample. Very importantly, the uremic toxins can be classified as those that dissolve readily in water water soluble and those that do not (these are fat soluble). Normal renal function (and dialysis) affects removal of water soluble solutes. However, water soluble solutes of any sizes may bind to protein in plasma or on the cell surface protein bound. If these were in free form they might be dialyzed but the bound forms are not dialyzed since the dialyzer membranes are not permeable to proteins. Uremia toxins of any type or size are likely to also bind to and in tissues tissue bound form. Obviously the tissue bound form is not immediately accessible for removal by dialysis.



Urea has remained the most commonly used chemical marker of impaired renal function and uremia. Also, the kinetics of urea is relatively readily definable without complicated models e.g., the volume of urea distribution approximates body water and urea diffuses readily throughout this volume. Since urea is the most abundant end-product of protein metabolism, and the generation side of the urea kinetic equation provides potentially useful information regarding protein nutrition, further advocates Urea as a marker. However, as is increasingly recognized, the correlation between blood urea concentration and the severity and scope of uremic toxicity is incomplete. Effectively, uremic toxicity cannot be summarized by the concentration of a single, small solute and urea measurement and definition of urea kinetics is limited for full quantification of dialysis efficiency. Unfortunately, there is no consensus for an alternative marker so urea and its kinetic analysis remain our best attempt at dialysis quantification. There is an interesting Website EuTox.com that identifies new Uremic Toxins that you might find interesting to visit. The important consideration is that we still dont know all the uremic toxins we do know that Normal renal function clears at the Glomerular level substances up to almost 70,000 Daltons MW inferring that if we are to replace renal function by dialysis we need to mimic this to some degree.

Not Dialyzable

Classification of Uremic Toxins


For exclusive use of Lualhati, Anna Lourdes 25 PRINCIPLES OF DIALYSIS Hemodialysis uses principally the processes of diffusion, ultrafiltration and convection. Diffusion (movement of solute from an area of high to low solute concentration) requires a concentration gradient of the solutes this is achieved by the:

1. Qb and the Qd rates, 2. Dialyzer membrane (semi permeable pore size that allows the particular solute to pass through

the membrane) 3. Surface Area of the dialyzer 4. Thickness of the dialyzer membrane 5. Temperature for kinetic movement 6. Time along the membrane for concentration difference recognition and for action 7. Counter-current flow of dialysate and blood; flow geometry optimizing the opportunity for diffusive

process


For exclusive use of Lualhati, Anna Lourdes 26 Ultrafiltration is the movement of fluid across a semi-permeable membrane from an area of high to low pressure. This process is achieved partly by the Hemodialysis machine applying negative (vacuum) pressure on the dialysate side of the circuit and secondly the hydraulic nature of the dialyzing membrane (KUF).

Convection is the movement of solutes with the fluid floe (solvent drag) the movement of membrane permeable solutes with ultrafiltrated fluid. This process of solute transport is effective for solutes up to and including 40,000Da MW.

(Hemo Dia Filtration) - a combination of diffusive and convective processes has been the focus for more effective (efficient) dialysis as it mimics more closely the renal transport and fluid processes. It is now recognized that Diffusive process are important for small molecular weight substances (e.g. Urea, Creatine), while Filtration (convective process) are important for the Middle to larger MW solutes (e.g. B2Microglobulin, iPTH, and a number of the inflammatory mediators Uremic toxins). Therefore a combination of the 2 processes is a logical conclusion. HEMODIALYSIS Chronic hemodialysis has been in practice for more than 40 years and although we have increased understanding and practice of hemodialysis there remains some challenges to dialysis clinicians. Conventional hemodialysis does not mimic well the homeostatic functions of the kidneys, with short intermittent dialysis resulting in swings of solutes and fluid and resultant patient symptoms contributing to the increased morbidity (short term) and mortality (long term).


For exclusive use of Lualhati, Anna Lourdes 27 Thereby some of the challenges in practice include more effective management of clients fluid status, protection and management of cardiovascular risks, nutrition, biocompatibility, improved vascular access survival and more effective measures of dialysis adequacy. One strategy that has evolved over the past decade is that of enhanced dialysis or daily dialysis, with some promising early results, however this approach also needs increased research and analyzed by clinical effectiveness and health economic measures. THE HEMODIALYSIS MACHINE The Hemodialysis has evolved over the history of dialysis; increasing its safety and reliability significantly. Clinical staff needs to understand the functioning of the machine in order to mange it safely and also the patient.

THE EXTRACORPOREAL CIRCUIT



The role of Albumin

Qb and Negative Pressure

Effective blood flow= F * nominal blood flow

0-100-200-300-400-500-600-700

Pre-pump pressure [mm Hg]

0

20

40

60

80

100Effective Qb in % of nominal Qb

ARE YOU DELIVERING THE PRESCRIBED Qb?

The role of Albumin

Monitoring pressures

Dialyzer

Arterial drip chamber

Anticoagulant

Arterial blood pumpPart

monitor

Pressure transducer protector Arterial needle

Pvenmonitor

Pressure transducerprotector

Air detector

Venous drip chamber

Venous line clamp

Venous needle

Thrombus filter

pump P

negative pressure

higher positive pressure

lower positive pressure


For exclusive use of Lualhati, Anna Lourdes 29 ULTRASONIC AIR DETECTORS

THE FLUID FLOWS & HYDRAULICS



THE BALANCING CHAMBER CRITICAL ADDITION IN THE CONTEMPORARY HEMODIALYSIS MACHINE

CYCLE 1 CYCLE 2



SAFETY & USER FRIENDLINESS BLOOD CIRCUIT ALARM

Audio Visual Blood pump stops Line clamp activated

DIALYSATE CIRCUIT ALARM

Audio Visual Bypass

USER FRIENDLINESS


For exclusive use of Lualhati, Anna Lourdes 33 Summary

The next section of the course analyses methods and strategies for achieving fluid balance as well as determining the clients Ideal Dry Weight and the justification for focusing on fluid homeostasis in the ESRD population. THE RELATIONSHIP OF FLUID, HYPERTENSION AND CVD

REQUIREMENTS FOR HEMODIALYSIS The requirements for hemodialysis include:

1. Dedicated staff that are trained to understand the technologies and the needs of the patients 2. Hemodialysis machines; ensure the extracorporeal and dialysate circuits deliver and ensure

safety of the patient at all time 3. Dialyzer membrane that is predictable and reliable ; biocompatible as much as possible 4. Vascular access; Chronic access (AVF, AVG) 5. Water Treatment System 6. Dialysate management; In-house, on-line or liquid (manufactured) 7. Standard Operating Procedures (SOPs, Clinical Policies & procedures) 8. Infection Control Standard Precautions (Dialysis) 9. Patient Management (Clinical Management Systems) Long term management 10. Documentation and Surveillance System to ensure quality; CQI, Clinical Management System



11. Rehabilitation program; long term outcomes & 12. Patients

DIALYZER MEMBRANES Dialyzer membranes, because of their close proximity to patients blood need to be as biocompatible as possible; current, contemporary dialyzer membranes are synthetic; Polysulfone, polyacrylonnitrile and Polyamide. The functions we require to achieve with a dialyzer are essentially two solute exchange between blood and dialysate and fluid removal from the patient. At its most basic a dialyzer is an exchanger designed to permit the exchange of water and solutes between blood and a physiological electrolyte solution dialysate.

The functions that need to be contained in dialyzers


For exclusive use of Lualhati, Anna Lourdes 35 These exchange functions occur across the dialyzer membrane which is designed and fabricated for selective permeability. It follows that the minimum requirements for a dialyzer include a membrane which separates a blood flow path or channel from a dialysate flow channel. Both blood and dialysate flow channels need entry and exit ports. All of these components are contained in a casing or casket (also called housing). The arrangement of the components within the casing is such that the flow paths for blood and dialysate are separated by a sealing process known as potting. In the diagram below, the arrangement of the membrane as hollow-fibers is shown, providing a flow path for blood within the lumens of the fibers and a flow path round the fibers for dialysate is shown here in longitudinal and cross section.

The role of Albumin

Hollow Fibre dialyzers

dialysate path

blood path

membrane

long sectioncross section

Diagram showing the blood and dialysate flow paths



COMPONENTS OF THE CONTEMPORARY DIALYZER (FX-Dialyzer) Dialyzer membranes are categorized by the term flux low flux, high flux. The term flux as applied to dialyzer membranes correctly refers to their permeability to water defined by the measurable ultrafiltration coefficient (KUF) of the dialyzer. In units KUF is mL of water (filtrate) flow per 1 mmHg difference in hydrostatic pressure across the membrane (transmembrane pressure: TMP) per hour mL.mmHg-1.hour1. The KUF of the dialyzer membrane is determined by the proportion of the membrane that has open pores the product of pore density and average pore size. Although not fully standardized, the terms low, middle, high and super flux approximate the KUF values shown in picture below. If KUF is normalized to surface area of membrane in the dialyzer and assuming a fairly standard pore density per unit area, KUF is proportional to pore size. It follows that larger solutes will diffuse across higher KUF membranes more readily than membranes with lower KUF. When referring to solute clearing capacity of membranes and dialyzers we should refer to a grading of their solute permeability low, medium, high.

During dialysis there are three relevant pressures the hydrostatic pressure of dialysate, the hydrostatic pressure of blood and the oncotic pressure of blood. The dialyzer during dialysis is dynamic regarding all these pressures.

1. The dialysate is pumped or drawn from the dialyzer (the dialysate pump operates downstream of the dialyzer). Relative to zero pressure, the pressure at the dialysis outlet is more negative than the pressure at the dialysis inlet because pressure is dissipated (lost) due to resistance to dialysate flow through the dialyzer.

2. Blood is pumped through the dialyzer (the blood pump operates upstream of the dialyzer). The pressure in blood (in the fibres) is maximum at the blood inlet and dissipates due to resistance to flow along the length of the fiber.



3. Oncotic pressure due to the action of plasma proteins is lowest at the blood inlet but because of removal of fluid and concentration of proteins rises towards the blood outlet. If all these pressure changes were changing linearly along the length of the dialyzer the average or net transmembrane pressure (TMP) would be as represented by the formula in diagram below. Linear change is a good approximation for dialysate pressure but the changes in the blood and oncotic pressures are not linear and not exactly predictable.

The role of Albumin

Dialyzer hydraulic permeability

BloodIN

DialysateOUT

BloodOUT

DialysateIN

PBin

PDinPDout

PBoutBin Bout

Relative to zero TMPPDout < PDinPBin > PBoutBout > Bin

TMP [(PBin + PBout )/2]-[(PDout + PDin)/2]-[(Bout + Bin )/2]

Modern dialyzers may have KUF in excess of 40 mL mmHg-1.hour-1. A difference of 20 mmHg in TMP would mean a difference in UF of 800 mL per hour or > 3L in a session of 4 hours. That would create serious problems for the patient. For this reason modern dialysis systems do not create a TMP to determine ultrafiltration. They remove a precise volume of dialysate from a dialysate hydraulics that is effectively a closed system where dialysate inflow and outflow are exactly balanced and equal (will be explained in detail in later modules). In such a system removing some of the dialysate forces an equal volume to be replaced in the dialysate circuit by a flow of fluid across the membrane from the patients blood. At a point along the dialyzer length the pressures reverse and there is zero TMP and no filtrate flow. Beyond that point the dialysate pressure now exceeds the pressure in the fiber and water flows from the Dialysate into the fiber and effectively into the patients blood. This is the phenomenon of back filtration. The point along the length of a dialyzer where the pressures reverse is the isobaric (equal pressures) distance or length and will vary depending upon the set UF (at the UF pump) and the membranes water permeability. Moreover, the isobaric point changes during dialysis due to changes in the patients blood density, protein content and oncotic pressure resulting from removal of plasma water from the blood. At any set value for UF the isobaric point is further from the blood inlet end as water permeability of the membrane (~ dialyzer KUF) falls and nearer to the blood inlet as KUF rises. Thus, at any set UF back-filtration is larger for high flux compared to low flux dialyzers. For any set membrane water permeability (KUF) the isobaric point is further from the blood inlet as UF rises and nearer to the blood inlet for lower UF. Thus, back-filtration is always higher when the UF goal is lower.



The role of Albumin

Backfiltration

Pres

sure

mm

Hg

DP HF-net

Forward filtration

Back filtration

Isobaric point

Lower set UFHigher KUF

Higher set UFLower KUF

The term internal filtration is used to describe this phenomenon which occurs almost invariably with modern dialyzers. The filtrate formed at the blood inlet end is drained to the dialysate outlet. The dialysate that enters the blood flow in the capillary comes mainly from the fresh dialysate at the dialysate inlet and joins the blood leaving the dialyzer; what is happening is a version of post dilution-hemodiafiltration. Some of the volume of filtration formed at the blood inlet end of the dialyzer is replaced by dialysate at the blood outlet end.

The role of Albumin

Internal filtration

BloodIN

DialysateOUT

BloodOUT

DialysateIN

Isobaric point



SUMMARY POINTS & DIALYZERS (MEMBRANES)


For exclusive use of Lualhati, Anna Lourdes 40 DIALYSIS DOSE & ADEQUACY OF DIALYSIS How much dialysis is enough? We have just discussed the benefits, especially related to the cardiovascular system, of daily more frequent dialysis. The Clinical Practice Guidelines (CPGs) advocate an achieved spKt/V of at least 1.3 (1.4) (See http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_uptoc.html#hd hemodialysis Adequacy Guidelines). Gotch and colleagues were the originators of the formula for determining Adequacy of dialysis through Kt/V calculation (See Gotch and Port commentary on the HEMO study). The Kt/V equation formulation has a basis in Pharmacokinetics, with clearance (K) and volume distribution (V) integral to the calculation. There remain a number of controversies related to Dose/Adequacy of dialysis including: -

Relationship of V to clinical outcomes: as the denominator of the equation as V increases the calculated Kt/V diminishes. Thereby as the client increases weight their Kt/V decreases, however clinically they may be doing well, eating and gaining body weight. However a client who is eating more is also generating greater amounts of nitrogenous wastes, and unless these are removed, over time they will eventually impact on the clients overall well being.

Often the disparity between the Kt/V result and clinical presentation and client history: there could be a lag time related with the estimation of clearance and the clients signs and symptoms.

The blood sampling method to determine the calculated Kt/V is also fraught with errors. Kt/V is based on small molecular weight (MW) solute clearance (Urea kinetics) and the question

remains as to whether this is the marker to determine dosing and adequacy of dialysis or whether middle MW solute clearance should also be measured:

Thereby there remain some issues in practice regarding the Dialysis Dose and Adequacy of dialysis. Much of the current focus in the improvement of dialysis is related to determining the significant components of Uremia that require correction or modification to improve the clinical effectiveness and optimal client outcomes.

Websites related to Dose of Dialysis/Adequacy of Dialysis: - http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_uptoc.html#hd KDOQI Adequacy Guidelines http://www.cari.org.au/dialysis_adequacy_publ2000.php CARI Adequacy CPG (Australian) http://www.hdcn.com/calc.htm Calculation tools (HDCN website) http://www.ndt-educational.org/guidelines.asp European Best Practice Guidelines

Overview Readings: - De Palma JR. and Pittard JD. (2001) Dialysis dose (Part 1). Dialysis and Transplantation. April. PP. 251 - 260. De Palma JR. and Pittard JD. (2001) Dialysis dose (Part 2). Dialysis and Transplantation. May. PP. 315 -.323. Fresenius Medical Care Asia Pacific CDPB112013

For exclusive use of Lualhati, Anna Lourdes 41 Leading Authors: - Charra B. (2001) Is Kt/V urea a satisfactory measure for dosing the newer dialysis regimens? Seminars in Dialysis. Vol. 14,1, pp. 8-9. Lindsay RM and Sternby J. (2001) Future directions in dialysis quantification. Seminars in Dialysis. Vol. 14, 4, pp. 300-307. Syme, SW, Hootkins RE and Will EJ. (1998), solute clearance and tissue clearance times. Seminars in Dialysis. Vol. 11, 3, pp. 185 188. Other readings: - Goodkin, DA, Mapes, DL and Held, PJ. (2001). The dialysis outcomes and practice patterns study (DOPPS): How can we improve the care of hemodialysis patients? Seminars in Dialysis. Vol. 14, 3, pp. 157 159. EQUATIONS: Also see the Adequacy PowerPoint for more details together with the readings and Text. Besides URR, these formulae are easy to compute in your PDA, Scientific calculator or computer.

1. URR (Urea Reduction Ratio) URR = {Pre dialysis Urea Post dialysis urea} X 100

Pre dialysis Urea The URR remains the most frequently used measure of Dialysis Dose due to ease of calculation and understanding. The CPGs advocate a minimum URR of > 65% (70% by the CARI guidelines)

2. LINEAR FORMULA

Kt/V = 2.2 (3.3 X [R {0.03 UF/W}]) R = post Urea/Pre Urea UF = pre dialysis weight post dialysis weight W = post dialysis weight

This formula considers that there is a linear relationship between the R and Kt/V. This assumption is not correct, however the Kt/V can be easily calculated and provides a rough estimate.

3. LOGARITHMIC FORMULA This is Daugirdas equation that is utilized in most Dialysis programs.

Kt/V = (-In [R 0.008t]) + ([4-3.5 R] X [UF/W]) In = natural logarithm (e on Scientific calculator)

t = duration of dialysis in hours R = post Urea/Pre Urea UF = pre dialysis weight post dialysis weight W = post dialysis weight

4. CORRECTION FOR 2-POOL (Double Pool) Adjusting for the Rebound


For exclusive use of Lualhati, Anna Lourdes 42 The two formulae for estimating the equilibrated Kt/V (eqKt/V) from the unequilibrated single pool Kt/V (spKt/V) are adjusting the spKt/V result for the rebound that occurs some 30 - 40 minutes post dialysis as the urea and other solutes equilibrate between the Extracellular (Vascular and Interstitial) and Intracellular compartments (hence the terminology equilibrated). The correction factor is further adjusted for the type of vascular access; venous (Central Venous Dialysis Catheter) and the conventional arterio-venous access (AVF and AVG): -

A-V vascular access: eqKt/v = Kt/V (0.6 x [{Kt/V}/t]) + 0.03 CVDC (venous): eqKt/V = Kt/V (0.4 X [{Kt/V}/t] + 0.02

Why is there need for the adjustment related to the type of vascular access? Discuss spKt/V and eqKt/V as effective measures for clearance/adequacy. Another consideration when prescribing dialysis dose, is not just the solute clearance but also effective fluid clearance. Fluid imbalance associated with ESRD, contributes to clients hypertension and over time LVH (Left Ventricular Hypertrophy) linking to their Cardiac morbidity and mortality risk. Considering the need for fluid homeostasis becomes a critical component of clinical management, both in the short and long term survival of ESRD population. We will be discussing this further in the Fluid Management and Assessment section. Vascular Physiology & Long Term Survival of Vascular Accesses in RRT Hemodialysis therapy is reliant on the adequacy of a vascular access. Optimal clearance associated with dialysis relies on the Dialysate flow rate, membrane permeability and surface area, dialysis time and the blood flow rate through the dialyzer. The Qb is dependent on the vascular access flow rate for clearance and mimics the relationship between renal blood flow, filtration (at the Glomerulus) and opportunity for clearance; diminished Glomerular blood flow results in a reduction in GFR and clearance. Dysfunctional vascular access will thereby adversely affect dialysis adequacy and result in increased patient morbidity and mortality. Nurses are integral in managing the vascular accesses to assure both the adequacy of dialysis and survival of the access. Various vascular accesses are used for hemodialysis procedure, including: -

1. Percutaneous vascular access; Jugular, Femoral or Subclavian vein catheters, which are used either temporarily or permanently.

2. Arteriovenous Fistula (AVF) or Grafts (AVG). The AVF is the preferred vascular access, with evidence of long-term survival, reduced complications and improved flow rates, compared to the other options.12 The challenges with vascular access care for the dialysis clinical team, relate to: -

Creation of the vascular access (Surgeon or Interventionist Nephrologist or Nurse Practitioner (evolving role); especially in patients with peripheral vascular disease, elderly patients and those with diabetes mellitus.



Maintenance of the vascular access; increasing survival, reducing complications (thrombosis, stenosis, aneurysm)

Reducing the pain associated with cannulation. Increasing the predictability and reliability of successful access to the vascular access blood flow. Effective utilization of vascular access for daily more frequent dialysis (contemporary approach to

achieving more homeostatic management of fluid, electrolyte and uremic waste clearance). VASCULAR ACCESS ASSESSMENT The patients arterial, venous and cardiopulmonary system determines the most viable access for the patient. The assessment includes: -

History; Previous sited vascular accesses; Central catheter history; Pacemaker; Congestive heart Failure; Peripheral Vascular Disease; Diabetes and associated vessel disease.

Physical examination Doppler evaluation Scheduling of vascular access creation; Preservation of peripheral vessels by avoiding

venipunctures. AVF construction at least six months prior to anticipated commencement of dialysis, based on the trend of rising plasma Creatinine. Ideal referral to vascular surgeon when serum Creatinine around 400mol/L (4mg/Dl).

Activity 1; Develop a strategy for the preparation of patients for vascular access. It may be

useful to incorporate an algorithm related to their morbidity and risk status and relate to selection of dialysis vascular access.

Activity 2: Regarding vascular assesses summarize the benefits for the various vascular

accesses used for hemodialysis. It would also be useful to group the patient population under the following

categories: Elderly, Diabetes and Cardiovascular disease. Analyze AVF and AVG and the KDOQI Vascular access CPGs and develop a

framework for selection and management of these vascular accesses. Percutaneous hemodialysis catheter utilization is quite prevalent in practice What

are the practices that are used to reduce complications? Define the following terms:

AV Fistula ______________________________________________________________________________________________________________________________ AV Graft ______________________________________________________________________________________________________________________________ Aneurysm ______________________________________________________________________________________________________________________________ Bruit ______________________________________________________________________________________________________________________________


For exclusive use of Lualhati, Anna Lourdes 44 Infiltration ______________________________________________________________________________________________________________________________ Pseudo aneurysm ______________________________________________________________________________________________________________________________ Recirculation ______________________________________________________________________________________________________________________________ Stenosis ______________________________________________________________________________________________________________________________ Thrill ______________________________________________________________________________________________________________________________ Thrombosis ______________________________________________________________________________________________________________________________

CLINICAL OUTCOMES IN DIALYSIS - CLINICAL INDICATORS

1. Anemia Management

a. Hb level 11-12 gm/dL b. TS% 22-50

2. Bone Management a. Phosphate pre dialysis < 5.5 (5.0) gm/dL b. Calcium 8.8 9.8 mg/dL c. iPTH d. Calcium X Phosphate

3. Fluid and BP control a. Interdialytic fluid gains < 3-5% of EDWt b. BP normalized 140/80 mmHg 160/80-90 mmHg)

4. Nutrition a. Albumin level b. nPNA c. HCO3

5. Adequacy of HD a. spKt/V 1.4 (3 sessions per week) b. More frequent dialysis sessions c. Convective therapies - OL-HDF d. Diabetic population needs


For exclusive use of Lualhati, Anna Lourdes 45 ANAEMIA MANAGEMENT The challenges in Renal Anemia management focus on achieving the target 11-12 g/dL Hemoglobin in the most cost-effective manner. Understanding the factors contributing to the Anemia, as well as those that impact on erythropoiesis aids in the effective management. The predominant cause of anemia in CKD is reduced or insufficient production of Erythropoeitin (EPO) other factors include Iron deficiency and Vitamin B12 and folate deficiency. Correcting the anemia has been found to have a significant impact on cardiovascular well-being as well as Health related quality of life. Thereby Therapy should be targeted at the following: -

Replacement of EPO (individualized) Iron therapy (usually IV; KDOQI, CARI) Vitamin B and folate replacement.

When assessing the effectiveness of treatment and/or poor response the following should also be assessed:

Nutrition and overall well-being Active Inflammatory condition Adequacy of dialysis Renal Osteodystrophy; Osteitis Fibrosa associated with Secondary hyperparathyroidism

KDOQI GUIDELINES ANEMIA MANAGEMENT

http://jasn.asnjournals.org/content/14/10/2654/F1.expansion.html


For exclusive use of Lualhati, Anna Lourdes 46 RENAL OSTEODYSTOPHY Renal Osteodystrophy begins in the mild to moderate phase of CKD and continues to be the Achilles heel in management of ESRD. The contributing factors to the raised iPTH, leading to Osteitis Fibrosa includes: -

Reduced effective 1,25 DHCC Raised serum phosphate Reduced ionized calcium Raised iPTH

Dialysis thrice weekly is not very effective at controlling the phosphate; however success has been reported with enhanced dialysis therapies, clearing the phosphate before it can settle in the intracellular compartment. Management of bone disease incorporates the following, titrated to the individual: -

Phosphate binders; Calcium, cationic polymer, Aluminum and compounds. Vitamin D therapy; results problems in management = hypocalcaemia (action of Vitamin D) and

high calcium phosphate product with increased risk of metastatic calcification. Parathyroidectomy Auto implant of Parathyroid gland



Serum phosphate (Pi, PO4) should be measured every 4-12 weeks to adjust therapy with phosphate binders. This can be done using the phosphate algorithm below:

http://renux.dmed.ed.ac.uk/edren/Handbookbits/HDBKosteodyst.html#PO4

Also Visit: http://www.kidney.org/professionals/kdoqi/guidelines_commentaries.cf

CARDIOVASCULAR (Blood Pressure and Fluid Management) The cardiovascular risk for ESRD patients relates to more than just fluid imbalance and hypertension, although it is critical to address these aspects. There are some interesting early results with pharmaceutical agents STATINS, which besides lowering and controlling the dyslipidaemia appear to offer further cardiac protection. Other factors that should be considered in care planning include:

Adequacy of dialysis Biocompatibility Exercise Nutrition Anemia correction Effective management of calcium, iPTH and phosphate


For exclusive use of Lualhati, Anna Lourdes 48 FACTORS IMPLICATED IN THE PATHOGENESIS OF HYPERTENSION IN ESRD TARGET:

TARGET: REDUCE INFLAMMATION (Adequacy of dialysis, Clearance of Uremic toxins, Biocompatibility)


For exclusive use of Lualhati, Anna Lourdes 49 HYPERTENSION MANAGEMENT SCHEMA 20

Regular nutritional assessment of ESRD patients is paramount to ensuring optimal well-being and evaluation of the adequacy of the RRT. The ESRD population is at risk of malnutrition can be related to appetite and reduced intake, increased protein catabolism and finally due to losses > intake. The peritoneal dialysis population is at a greater risk of the latter, due to changes in the permeability of the peritoneum exacerbated by episodes of peritonitis. NUTRITIONAL ASSESSMENT APPROACH The KDOQI Nutritional CPGs advocate undertaking a nutritional assessment (Subjective Global Assessment SGA), at least every six months, unless there are indicators to further initiate an assessment. The nutritional assessment of ESRD patients includes the following:

History Symptoms of nausea, vomiting and anorexia, recent changes in body weight. Presence of chronic diseases, Diabetes, GIT disturbances, depression and CVD.

Assessment of food intake Analysis of patients diet recall. Organize patient to document food intake for at least 2 days.

Physical examination Assessment of muscle and fat stores; upper and lower body comparison.

Biochemistry Serum Albumin, acute phase proteins (C reactive protein), Urea, nPNA, phosphate and potassium.



Anthropometrics and Bioimpedence

1. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016.

2. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575.

3. Ozkahya M, Toz H, Qzerkan F, et al. Impact of volume control on left ventricular hypertrophy in dialysis patients. J Nephrol. 2002; 15:655660.

4. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351:12961305.

5. Grooteman MP, Nube MJ, Daha MR, et al. Cytokine profiles during clinical high-flux dialysis: no evidence for cytokine generation by circulating monocytes. J Am Soc Nephrol. 1997; 8:17451754.

6. Sitter T, Bergner A, Schiffl H. Dialysate related cytokine induction and response to recombinant human erythropoietin in hemodialysis patients. Nephrol Dial Transplant. 2000; 15:12071211.

7. Schindler R, ChristKohlrausch F. et al. Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens. Clin Nephrol. 2003; 59:447454.

8. Merello Godino JI, Rentero R, Orlandini G, et al. Results from EuCliD (European Clinical Dialysis Database): impact of shifting treatment modality. Int J Artif Organs. 2002; 25:10491060.





13. Ozkahya M, Toz H, Qzerkan F, et al. Impact of volume control on left ventricular hypertrophy in dialysis patients. J Nephrol. 2002; 15:655660.


For exclusive use of Lualhati, Anna Lourdes 51 KDOQI GUIDELINES FOR ESRD PATIENTS



Food intake factors in uremia

Adequate (not excess)balanced diet

Adequate access to nutrients

Appetite, hunger& satiety

NUTRIENT NEEDS

cdp b_lualhati, anna lourdes (1)_norestriction

Documents